Gesualdo's family had acquired the principality of Venosa in 1560. He was born on March 30, 1566; 3 years after his older brother Luigi.[1] His uncle was Carlo Borromeo, later Saint Charles Borromeo. In addition, Gesualdo's mother, Geronima Borromeo, was the niece of Pope Pius IV. Most likely he was born at Venosa, then part of the Kingdom of Naples, but little else is known about his early life. "His mother died when he was only seven, and at the request of his uncle, Carlo Borromeo for whom he was named, he was sent to Rome to be set on the path of an ecclesiastical career. There he was placed under the protection of his uncle, Alfonso (d.1603), then dean of the College of Cardinals, later unsuccessful pretender to the papacy, and ultimately Archbishop of Naples."[1] His brother Luigi was to become the next Prince of Venosa due to hereditary laws, but after his untimely death in 1584, Carlo became the eighth Count of Conza and the third Prince of Venosa.[1] Gesualdo had a musical relationship with Pomponio Nenna, though whether it was student to teacher, or colleague to colleague, is uncertain. Regardless of this, however, he had a single-minded devotion to music from an early age, and showed little interest in anything else. In addition to the lute, he also played the harpsichord and guitar.[2]

In 1586 Gesualdo married his first cousin, Donna Maria d'Avalos, the daughter of the Marquis of Pescara. Two years later she began a love affair with Fabrizio Carafa, the Duke of Andria. Evidently, she was able to keep it secret from her husband for almost two years, even though the existence of the affair was well known elsewhere. Finally, on October 16, 1590, at the Palazzo San Severo in Naples, when Gesualdo had allegedly gone away on a hunting trip, the two lovers took insufficient precaution at last (Gesualdo had arranged with his servants to have keys to the locks of his palace copied in wood so that he could gain entrance if the doors were locked). Gesualdo returned to the palace, caught them in flagrante delicto and murdered them both in their bed. Afterward, he left their mutilated bodies in front of the palace for all to see. Being a nobleman he was immune from prosecution, but not to revenge, so he fled to his castle at Venosa where he would be safe from any of the relatives of either his wife or her lover.

Details on the murders are not lacking, as the depositions of witnesses to the magistrates have survived in full. While they disagree on some details, they agree on the principal points, and it is apparent that Gesualdo had help from his servants, who may have done most of the killing; however, Gesualdo certainly stabbed Maria multiple times, shouting as he did, "she's not dead yet!" The Duke of Andria was found slaughtered by numerous deep sword wounds, as well as by a shot through the head. When he was found, he was dressed in women's clothing (specifically, Maria's night dress). His own clothing was found piled up by the bedside, unbloodied.

The murders were widely publicized, including in verse by poets such as Tasso and an entire flock of Neapolitan poets, eager to capitalize on the sensation. The salacious details of the murders were broadcast in print, but nothing was done to apprehend the Prince of Venosa. The police report[4] from the scene makes for shocking reading even after more than four hundred years.

Accounts on events after the murders differ. According to some sources, Gesualdo also murdered his second son by Maria, who was an infant, after looking into his eyes and doubting his paternity (according to a 19th-century source he "swung the infant around in his cradle until the breath left his body"); another source indicates that he murdered his father-in-law as well, after the man had come seeking revenge. Gesualdo had employed a company of men-at-arms to ward off just such an event. However, contemporary documentation from official sources for either of these alleged murders is lacking.

By 1594, Gesualdo had arranged for another marriage, this time to Leonora d'Este, the niece of Duke Alfonso II. In that year Gesualdo ventured to Ferrara, the home of the d'Este court and also one of the centers of progressive musical activity in Italy, especially the madrigal; Gesualdo was especially interested in meeting (and evidently critiquing) Luzzasco Luzzaschi, one of the most forward-looking composers in the genre. Leonora was married to Gesualdo and moved with him back to his estate in 1597. In the meantime, he engaged in more than two years of creative activity in the innovative environment of Ferrara, surrounded by some of the finest musicians in Italy. While in Ferrara, he published his first book of madrigals. Also, he worked with the concerto delle donne, the three virtuoso female singers who were among the most renowned performers in Italy, and for whom many other composers wrote music.

In a letter of June 25, 1594, Gesualdo indicated he was writing music for the three women in the concerto delle donne; however, it is probable that some of the music he wrote, for example that in the newly developing monodic and/or concertato styles, has not survived.[5]

After returning to his castle at Gesualdo from Ferrara in 1595, he set up a situation similar to the one that existed in Ferrara, with a group of resident virtuoso musicians who would sing his own music. While his estate became a center of music-making, it was for Gesualdo alone. With his considerable financial resources, he was able to hire singers and instrumentalists for his own pleasure. He rarely left his castle, taking delight in nothing but music.[6] Most of his famous music was published in Naples in 1603 and in the castle of Gesualdo (with printer Giovanni Giacomo Carlino) in 1611, and the most notoriously chromatic and difficult portion of it was all written during his period of self-isolation.

The relationship between Gesualdo and his new wife was not good; she accused him of abuse, and the Este family attempted to obtain a divorce. She spent more and more time away from the isolated estate. Gesualdo wrote many angry letters to Modena where she often went to stay with her brother. According to Cecil Gray, "She seems to have been a very virtuous lady ... for there is no record of his having killed her."[7]

In 1600, Gesualdo's son by his second marriage died. It has been postulated that after this Gesualdo had a large painting commissioned for the church of the Capuchins at Gesualdo, showing Gesualdo, his uncle Carlo Borromeo, his second wife Leonora, and his son, underneath a group of angelic figures; however, some sources suspect the painting was commissioned earlier, as the identity of the child is unclear.

Late in life he suffered from depression. Whether or not it was related to the guilt over his multiple murders is difficult to prove, but the evidence is suggestive. According to Campanella, writing in Lyon in 1635, Gesualdo had himself beaten daily by his servants, keeping a special servant whose duty it was to beat him "at stool",[4] and he engaged in a relentless, and fruitless, correspondence with Cardinal Borromeo to obtain relics, i.e., skeletal remains, of his uncle Carlo, with which he hoped to obtain healing for his mental disorder and possibly absolution for his crimes. Gesualdo's late setting of Psalm 51, the Miserere, is distinguished by its insistent and imploring musical repetitions, alternating lines of monophonic chant with pungently chromatic polyphony in a low vocal tessitura.

Gesualdo died in isolation, at his castle Gesualdo in Avellino, three weeks after the death of his son Emanuele, his first son by his marriage to Maria. One 20th-century biographer has suggested Gesualdo may have been murdered by his wife.[7] He was buried in the chapel of Saint Ignatius, in the church of the Gesù Nuovo, in Naples. The sepulchre was destroyed in the earthquake of 1688. When the church was rebuilt, the tomb was covered over, and is now under the pavement of the church. The burial plaque, however, remains.

The evidence that Gesualdo was tortured by guilt for the remainder of his life is considerable, and he may have given expression to it in his music. One of the most obvious characteristics of his music is the extravagant text setting of words representing extremes of emotion: "love", "pain", "death", "ecstasy", "agony" and other similar words occur frequently in his madrigal texts, most of which he probably wrote himself. While this type of word-painting is common among madrigalists of the late 16th century, it reached an extreme development in Gesualdo's music.

His music is among the most experimental and expressive of the Renaissance, and without question is the most wildly chromatic. Progressions such as those written by Gesualdo did not appear again in music until the 19th century, and then in a context of tonality.

Gesualdo's published music falls into three categories: sacred vocal music, secular vocal music, and instrumental music. His most famous compositions are his six published books of madrigals (between 1594 and 1611), as well as his Tenebrae Responsoria, which are very much like madrigals, except that they use texts from the Passion, a form (Tenebrae) used by many other composers. In addition to the works which he published, he left a large quantity of music in manuscript. This contains some of his richest experiments in chromaticism, as well as compositions in such contemporary avant-garde forms as monody. Some of these were products of the years he spent in Ferrara, and some were specifically written for the virtuoso singers there, the three women of the concerto di donne.

The first books of madrigals that Gesualdo published are close in style to the work of other contemporary madrigalists. Experiments with harmonic progression, cross-relation and violent rhythmic contrast increase in the later books, with Books Five and Six containing the most famous and extreme examples (for instance, the madrigals "Moro, lasso, al mio duolo" and "Beltà, poi che t'assenti", both of which are in Book Six, published in 1611). There is evidence that Gesualdo had these works in score form, in order to better display his contrapuntal inventions to other musicians, and also that Gesualdo intended his works to be sung by equal voices, as opposed to the concerted madrigal style popular in the period, which involved doubling and replacing voices with instruments.[2]

Characteristic of the Gesualdo style is a sectional format in which relatively slow-tempo passages of wild, occasionally shocking chromaticism alternate with quick-tempo diatonic passages. The text is closely wedded to the music, with individual words being given maximum attention. Some of the chromatic passages include all twelve notes of the chromatic scale within a single phrase, although scattered throughout different voices. Gesualdo was particularly fond of chromatic third relations, for instance juxtaposing the chords of A major and F major, or even C-sharp major and A minor (as he does at the beginning of [1]).

His most famous sacred composition is the set of Tenebrae Responsoria, published in 1611, which are stylistically madrigali spirituali—madrigals on sacred texts. As in the later books of madrigals, he uses particularly sharp dissonance and shocking chromatic juxtapositions, especially in the parts highlighting text passages having to do with Christ's suffering, or the guilt of St. Peter in having betrayed Jesus.

Mozart's C-Minor Piano Concerto was interrupted after the first movement, and a recording of some madrigals by Gesualdo took its place.

'These voices' I said appreciatively, 'these voices – they're a kind of bridge back to the human world.'

And a bridge they remained even while singing the most startlingly chromatic of the mad prince's compositions. Through the uneven phrases of the madrigals, the music pursued its course, never sticking to the same key for two bars together. In Gesualdo, that fantastic character out of a Webster melodrama, psychological disintegration had exaggerated, had pushed to the extreme limit, a tendency inherent in modal as opposed to fully tonal music. The resulting works sounded as though they might have been written by the later Schoenberg.

'And yet,' I felt myself constrained to say, as I listened to these strange products of a Counter-reformation psychosis working upon a late medieval art form, 'and yet it does not matter that he's all in bits. The whole is disorganized. But each individual fragment is in order, is a representative of a Higher Order. The Highest Order prevails even in the disintegration. The totality is present even in the broken pieces. More clearly present, perhaps, than in a completely coherent work. At least you aren't lulled into a sense of false security by some merely human, merely fabricated order. You have to rely on your immediate perception of the ultimate order. So in a certain sense disintegration may have its advantages. But of course it's dangerous, horribly dangerous. Suppose you couldn't get back, out of the chaos...'

Though Gesualdo's influence was exceptionally limited during his lifetime, his work has been rediscovered and appreciated as a precursor to later, equally expressive and technically difficult styles of music.

Italian singer-songwriter Franco Battiato wrote a song about him, Gesualdo da Venosa, from the album L'ombrello e la macchina da cucire (1995).

Musician Anna Calvi named Gesualdo as her ultimate cult hero quoting "Gesualdo was an Italian composer who, because of mental illness, murdered his wife and her lover, and wrote music in the 16th century that was so progressive and extreme that no one attempted to recreate his style until the 20th century... It wasn't until centuries later that he was rediscovered, and his work is a huge inspiration to me."[14]